Development and Persistence of Tissue-Level Musculoskeletal Deformity Following Brachial Plexus Birth Injury

臂丛神经出生损伤后组织水平肌肉骨骼畸形的发展和持续

• 批准号: 10838188
• 负责人: Jacqueline H Cole
• 金额: $ 7.99万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10838188
• 关键词: Affect; Animals; Articular Range of Motion; Biological; Birth trauma; Bone Density; Bone Injury; Brachial plexus structure; Characteristics; Clinical Treatment; Computer Models; Computer Simulation; Contracture; Data; Deformity; Development; Elements; Environment; Gait; Growth; Image; Impairment; Injury; Intervention; Joint structure of shoulder region; Limb Development; Limb structure; Location; Mechanics; Methods; Modeling; Morphology; Motion; Muscle; Musculoskeletal; Paralysed; Parents; Pattern; Property; Rattus; Research; Running; Structure; Surgical Disarticulation; Time; Tissues; Upper Extremity; Walking; Work; arm; bone; experience; humerus; insight; microCT; neuromuscular; parent grant; placebo group; postnatal period; response; scapula; spatiotemporal; timeline; tissue stress

Project Summary Brachial Plexus Birth Injury (BPBI) is a neuromuscular injury that causes lifelong arm impairments and deformities in the glenohumeral joint which restricts mobility of the upper limb. Little is known about the progression of bone and muscle growth in the postnatal period following BPBI. The parent grant explores key drivers of deformity progression including the timeline of development and resultant functional effects through a rat model consisting of different injury locations and unloading (preganglionic and postganglionic neurectomy, disarticulation, and sham groups). The primary hypothesis is that the key driver in BPBI bone deformity is the mechanical environment due to impaired longitudinal growth of paralyzed muscle and altered active functional loading beginning shortly after injury. The proposed work will further the parent research by investigating active loading of the glenohumeral joint during functional gait in a rat model. Bone readily adapts to its mechanical environment, so analysis of its organized microstructures would also provide insight to key mechanical drivers of microstructural deficits. Supplement Aim 1. Determine how limb loading is altered during functional gait following BPBI. Rationale: Spatiotemporal characteristics of gait are substantially and differentially altered during walking in rats following pre- and postganglionic neurectomy. However, the forces experienced on each limb at the ground and on the developing glenohumeral joint are unknown and are likely important drivers of glenohumeral development. Supplement Aim 2. Determine how active limb loading during functional gait drives morphological and microstructural changes in the glenoid. Rationale: Our unique co-simulation computational model of glenohumeral growth and function has been used to directly relate specific deformity and contracture features to isolated changes in passive muscle force, active range of motion, and biological growth rate; however, actual limb usage and its mechanical relationship to bone material properties and trabecular organization has not yet been explored. Altered gait and limb loading during walking and running after neurectomy will be evaluated to explore how limb usage and loading is affected by BPBI. Spatiotemporal motion data and ground contact forces will be recorded for each animal and compared among groups. Resultant gait data will be integrated into the computational simulation of glenohumeral loading and adaptation during active limb function following BPBI. Tissue properties will be validated using micro-computed tomography (micro-CT) images of the internal bone density and microstructure of the scapula and humerus collected under the R01 project and used to identify the portion of bone response due to active loading. A micro-CT-based micro-scale finite element model will provide tissue stress and yielding patterns to elucidate loading-driven adaptations in trabecular organization. The proposed supplement work will advance the originally planned modeling approach by including dynamic limb loads and new methods to actively predict bone material property changes and trabecular organization adaptations over the time of limb development.

项目摘要 臂丛神经出生损伤（BPBI）是一种神经肌肉损伤，导致终身手臂损伤， 盂肱关节畸形，限制上肢活动。很少有人知道的 BPBI后出生后骨和肌肉生长的进展。家长补助金探索关键 畸形进展的驱动因素，包括发育的时间轴和通过 由不同损伤位置和卸载（节前和节后神经切除术， 断节和假手术组）。主要假设是BPBI骨畸形的关键驱动因素是 由于瘫痪肌肉的纵向生长受损和主动功能改变而导致的机械环境 受伤后不久就开始负重。建议的工作将进一步通过调查积极的家长研究 在大鼠模型中功能性步态期间盂肱关节的负荷。骨骼很容易适应其机械 因此，对其组织结构的分析也将为关键的机械驱动因素提供洞察力。 微观结构缺陷。补充目标1。确定功能性步态期间肢体负荷如何改变 在BPBI之后。基本原理：步态的时空特征发生了实质性和差异性的改变 在大鼠的前和节后神经切除术后行走。然而，每个人所经历的力量 肢体在地面和发展中的盂肱关节是未知的，可能是重要的驱动因素， 盂肱发育补充目标2。确定在功能性步态期间主动肢体负荷 驱动关节盂的形态学和微观结构变化。理由：我们独特的共同模拟 盂肱关节生长和功能的计算模型已被用于直接关联特定畸形 和痉挛特征与被动肌肉力量、主动运动范围和生物学的孤立变化有关 生长率;然而，实际肢体使用及其与骨材料性能的机械关系， 小梁组织尚未被探索。步行和跑步时步态和肢体负荷的改变 将对神经切除术进行评估，以探索肢体使用和负荷如何受到BPBI的影响。时空运动 将记录每只动物的数据和地面接触力，并在组间进行比较。合成步态 数据将被集成到活动期间盂肱载荷和适应的计算模拟中 BPBI后的肢体功能。将使用微型计算机断层扫描（micro-CT）确认组织特性 在R01下收集的肩胛骨和肱骨的内部骨密度和显微结构图像 项目，并用于识别由于主动载荷引起的骨反应部分。一种基于微CT的微尺度 有限元模型将提供组织应力和屈服模式，以阐明 小梁组织拟议的补充工作将推进原计划的建模方法 通过包括动态肢体载荷和新方法来主动预测骨材料特性变化， 随着肢体发育，骨小梁组织的适应性变化。